Intoxication by the zinc protease botulinus neurotoxin A (BoNT-A) results from cleavage of a single Q-R bond in the neuronal protein SNAP-25, which disables the docking mechanism required for neurotransmitter release. In the present study, potential inhibitors of BoNT-A were assessed from their effects on the BoNT-A cleavage of a synthetic 17-mer peptide (SNAP-25, residues 187-203) spanning the Q-R cleavage site. Compounds that inhibited BoNT-A included thiols (zinc chelators) such as dithiothreitol, dimercaptopropanesulfonic acid, mercaptosuccinic acid and captopril. In addition, compounds containing multiple acidic functions, such as the SNARE motif V2 (ELDDRADALQ), the tripeptide Glu-Glu-Glu and the steroid glycoside glycyrrhizic acid, were effective inhibitors. 'Hinge' peptide mini-libraries (PMLs) having the structure acetyl-X(1)-X(2)-linker-X(3)-X(4)-NH(2) or X(1)-X(2)-linker-X(3), where X(1)-X(4) were mixtures of selected amino acids and the flexible linker was 4-aminobutyric acid, also provided effective inhibition. Targeted PMLs containing the acidic amino acids Asp and Glu, the scissile-bond amino acids Gln and Arg and the zinc chelators His and Cys produced pronounced inhibition of BoNT-A. Deconvolution of these libraries will provide novel ligands with improved inhibitory potency as leads in the design of peptide mimetics to treat BoNT poisoning.

Antitoxins↗

PubMedDate not supplied

The epidemiology of methicillin-resistant Staphylococcus aureus in a burn center.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in a critical care facility creates a multifaceted epidemiological problem in uncovering the source of infection. This study was undertaken to determine the true etiology of MRSA burn wound infections. Patients with a 30% or greater TBSA burn had both burned and unburned skin surface cultured upon admission, using RODAC plates. All other body fluids were cultured when sepsis was suspected. Admission cultures of 14 patients who developed MRSA wound infections were examined for methicillin-resistant organisms. Both admission isolates and infection isolates were compared by antibiogram analysis. Of the 14 patients admitted who developed MRSA infections, 57.1% of these had methicillin-resistant staphylococci present on admission. However, the remaining 42.9% of the patients had methicillin-sensitive, B-lactamase positive staphylococci present on admission. Isolates of group D streptococci resistant to methicillin were isolated in 35.7% of the patients. This data suggests that burn wound infections caused by MRSA very likely arise from the endogenous flora present at the time of injury through conferring the resistant plasmid by conjugational transfer.

Burn Units↗

PubMedDate not supplied